We propose to develop an integrated microchip platform for rapid, reliable and comprehensive diagnosis of cancer by examining the pathophysiological mechanism of tumor-immune interaction. This will be done at both molecular and cellular level. By applying this platform to analyze a large number of clinical samples, we expect to gain new insights about cancer immunobiology that point to new approaches for cancer prevention and treatment. During the K99 phase, I have demonstrated an Integrated barcode platform that can measure a large number of protein markers from small quantities of whole blood or from single cells. A panel of signaling proteins that have important implication in tumor inflammation has been integrated Into the microchip platform. In the ROO phase, I will further utilize this technology to Investigate the fundamental biology of tumor-immune interaction via measuring the paracrine signaling pathways between tumor and immune cells. I will also study the heterogeneity of tumor microenvironment by combining population dynamics modeling and the microchip-based molecular analysis. Once this model is trained with experimental or clinical data, it will become a useful tool to predict the outcomes or therapeutic responses of cancer patients. In addition, an on-chip culture of tumor cells and immune cells will be developed to emulate tumor microenvironment and then used for rapid, effective anti-cancer drug screening. To accomplish these goals, I will (1) use the Integrated barcode chip platform to study chronic Inflammation as a common mechanism in various human diseases and to reveal their correlations;(2) apply this tool to monitor the Immunological responses of cancer treatment;and (3) design a Tumor-on-a-Chip to re-engineer the tumorimmune Interactions ex vivo and use this platform for effective anti-cancer drug screening with rich feedback.
The proposed technology can be transformed into an Infomnative clinical tool to revolutionize the diagnoses of inflammatory cancers. It promises effective patient stratification for individualized treatment. It is also a versatile platform for a broad range of clinical applications such as immune monitoring and tracking the therapeutic responses of many human diseases.
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